Effects of block length on the enzymatic degradation and erosion of oxazoline linked poly-epsilon-caprolactone.

Abstract

The aim of the study was to develop enzyme sensitive polymers for pharmaceutical applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O) polymers were synthesized by using epsilon-caprolactone precursors with different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the effects of PCL block length on enzymatic degradation and erosion (weight loss) of PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22 days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O films occurred during incubation, and the erosion of the PCL-O films increased in parallel with a decrease in the PCL block length. The presence of the lipase inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the PCL-O films. These results indicate that lipase was mainly responsible for the enzymatic erosion of the PCL-O films. In comparison, practically no weight loss of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days incubation). The results demonstrate that the studied epsilon-caprolactone based poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be controlled by the PCL block length.

• Authors: Mika Pulkkinen, Minna Malin, Tommy Tarvainen, Tiina Saarimäki, Jukka Seppälä, Kristiina Järvinen
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 31 Issue 2 Pg. 119-28 (Jun 2007) ISSN: 0928-0987 [Print] Netherlands
• PMID: 17433634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,2'-bis(2-oxazoline)-linked poly(epsilon-caprolactone)
• Delayed-Action Preparations
• Drug Carriers
• Enzyme Inhibitors
• Lactones
• Polyesters
• ethylparaoxon
• Pancreatin
• Orlistat
• Lipase
• Paraoxon

Topics

• Delayed-Action Preparations
• Drug Carriers
• Drug Compounding
• Enzyme Inhibitors (pharmacology)
• Hydrogen-Ion Concentration
• Lactones (pharmacology)
• Lipase (antagonists & inhibitors, chemistry, metabolism)
• Molecular Weight
• Orlistat
• Pancreatin (chemistry, metabolism)
• Paraoxon (analogs & derivatives, pharmacology)
• Polyesters (chemical synthesis, metabolism)
• Solubility
• Surface Properties
• Time Factors